PB2129: COULD LYMPHOPENIA PREDICT OUTCOME OF PATIENTS WITH DIFFUSE LARGE B-CELL LYMPHOMA?
Authors: B. Merchan Muñoz, D. Subirá Pérez, M. I. Nuevo Lopez, M. Mora Argumanez, R. Pérez Alonso, A. Vazquez Ramo, A. Gil Perez, H. Guillen Garcia, J. Arbeteta Juanis, A. B. Santos Montero, N. Golbano Lopez, S. Herrero Lopez, M. D. Morales Sanz, D. De Miguel Llorente
Journal: HemaSphere (2022)

Background: The international prognostic index (IPI) is the standard clinical tool used to predict the outcome of patients diagnosed with diffuse large B-cell lymphoma (DLBCL). However, there is considerable heterogeneity within the IPI groups and immunochemotherapy (ICT) response. Surrogate markers of host immunity and more sensitive techniques to identify extranodal involvement could potentially be added to the IPI model to further improve it. Aims: To investigate whether absolute lymphocyte count (ALC), and peripheral blood and bone marrow (BM) infiltration using multiparametric flow cytometry immunophenotyping (MFC) may offer valuable information to predict prognosis in DLBCL. Methods: Eighty-eight patients diagnosed with DLBCL between 2014 and 2021 at a single centre were included in this study. Sixty percent of patients (n=53) had an intermediate-high or high IPI score-risk and 40% (n=35) showed low IPI score-risk. All ICT regimens included Rituximab. Median age of patients at diagnosis was 71 years (range, 24-90 years). After a median follow-up of 23.4 months (range, 2.8-99.5) complete remission (CR) without relapse was achieved by 66% of patients (n=58) and refractory disease or relapsed (R/R) was exhibited by 34% of patients (n=30). No differences were observed in median age, IPI or ICT administered in these two groups of patients. ALC was registered from complete blood cell count at diagnosis and after 2 months of ICT-ending, considering lymphopenia as ALC≤1´109/L in two determinations. Eight-color MFC analysed circulating lymphoma cells and BM infiltration. Chi square, Fisher’s exact test and t-test were used to compare patient’s characteristics, considering p<0.05 as statistically significant. Results: As it could be expected, IPI score showed impact on CR (p=0.013). Lymphopenia at diagnosis was associated with increased R/R DLBCL incidence (p=0.0001; figure 1). Besides, low ALC at diagnosis identified 9 patients within the low IPI group who did not achieve CR (p=0.001). This association was not observed in patients with high IPI score (p=0.102). Lymphocyte subtypes were studied by MFC in 41 patients: 83% (n=34) presented low B-cell counts and 17% (n=7) presented only low T and/or NK-cell counts. MFC detected circulating lymphoma cells in 17 out of 52 patients studied (33%). No correlation between the quality of response achieved and circulating lymphoma cells was recognized (p=0.141). BM infiltration was noticed in 31 patients (35%) at diagnosis: 6 were only detected by histopathology and 12 were only detected by MFC, showing minimal BM involvement (median 0.3%, range 0.01-3.3%). Three out of the 12 patients only detected by MFC (25%) would change to a higher IPI score-risk. Following the completion of first-line ICT, ALC normalization was observed in 43 patients (58%). Relapse and progression risk was significantly higher in patients with persistent low ALC (p=0.0037). Image:Summary/Conclusion: 1. Lymphopenia at diagnosis is an additional, inexpensive and easy value to predict relapse or refractory disease in DLBCL with low IPI score. 2. High resolution MFC improved the detection of BM infiltration, potentially affecting IPI score. However, circulating lymphoma cells did not offer additional prognosis information. 3. Persistent lymphopenia during routine follow-up after ICT-ending helps clinicians to identify patients who are more likely to relapse.